Gupta Lab Profile picture
Dec 17, 2021 7 tweets 3 min read Twitter logo Read on Twitter
Sharing some potentially significant findings relating to Omicron given the current situation. First of all huge thanks to the team working flat out- Bo Meng, @isabella_atmf and to our collaborators both in G2P, J2P along with @SystemsVirology. Findings as follows:
1. Omicron Spike protein mediates deficient cell entry and is inefficiently cleaved compared to Delta spike. We tested viral entry mediated by Wild Type, Delta and Omicron spikes using a pseudotyped virus system, infecting primary 3D lung alveolar organoids. Image
2. Omicron Spike protein induces relatively poor cell-cell fusion compared to WT and Delta. We expressed spike in cells stably expressing split GFP, so that Green signal could be measured over time upon cell-cell fusion and syncitia formation. The difference is significant. Image
3. What does this all mean? Efficient infection of lung cells could correlate with severity of lung disease. Syncitia or fused cells are often seen in respiratory tissues taken following severe disease. Delta was very good at both, in contrast to Omicron. Further work is needed
4. We also tested how well antibodies from vaccinated individuals neutralised Omicron v Delta. We found that Omicron was poorly neutralised after two doses of mRNA or Ad vectored vaccine compared to Delta, but that the third dose (mRNA vaccine) rescued this at an early time point Image
5. In summary this work suggests that Omicron does appear to have become more immune evasive, but that properties associated with disease progression *may* be attenuated to some extent. The significant growth of Omicron nevertheless represents a major public health challenge.
some more collaborator acknowledgements @JooHyeonLeeLab @Adamsizler Leo James and Guido Papa @MRC_LMB , Paul Lehner lab, and @Sci_Lipi

• • •

Missing some Tweet in this thread? You can try to force a refresh

Keep Current with Gupta Lab

Gupta Lab Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!


Twitter may remove this content at anytime! Save it as PDF for later use!

Try unrolling a thread yourself!

how to unroll video
  1. Follow @ThreadReaderApp to mention us!

  2. From a Twitter thread mention us with a keyword "unroll"
@threadreaderapp unroll

Practice here first or read more on our help page!

More from @GuptaR_lab

Oct 19, 2022
One of the major issues as we move through the pandemic is how we approach vaccination in the elderly, given severe outcomes are still occurring in this group. We have found that SARS-CoV-2 neutralisation following third dose is impaired in the elderly.…
Surprisingly, the impaired neutralisation was despite similar levels of anti spike IgG antibody concentrations in the blood when younger participants <70 were compared to those >70. This means that somehow younger people are making better antibodies and not simply more of them
When we looked more deeply at the B cells that make antibodies we found using single cell sequencing and flow cytometry that atypical spike specific memory B cells expressing surface markers CD11c and FCRL5 were significantly higher in the >70 population.
Read 7 tweets
Sep 30, 2022
Moving back to molecular virology, thrilled to be communicating our new paper on a topic close to our hearts: the virus-host interaction and involvement of cell cycle associated proteins.…
We found that productive SARS-CoV-2 infection induces cell cycle arrest and depletes cyclin D from infected cells. Surprisingly, cyclin D3 degradation induced by SARS-CoV-2 promoted infection not via cell cycle arrest, but by relieving cyclin interference with virion assembly.
Firstly, we found that following infection, Cyclin D1 and D3 translocated from nucleus into the cytoplasm for proteasomal degradation whilst cyclin A2 remained unaffected. Proteasome inhibition stabilized D-cyclins in and prevented relocalisation of cyclin D3 to the cytoplasm. ImageImage
Read 7 tweets
Sep 15, 2022
Our paper on NTD's role in TMPRSS2 usage/cell-cell fusion is out! N terminal domain is the interface for MERS CoV and its receptor. SARS-CoV-2 uses the receptor binding domain to bind ACE2 and the role of SARS-CoV-2 NTD is unclear.…
We had previously reported that the H69V70 deletion found in Alpha NTD increased spike mediated entry, and that Alpha was highly dependent on this deletion for infectivity and cell-cell fusion efficiency.…
We were interested in why Delta (B.1.617.2) outcompeted Kappa (B.1.617.1), given Kappa showed more immune evasion than Delta (…). We made a spike bearing Delta NTD in Kappa spike, and this increased entry in TMPRSS2 expressing lung cells and airway organoids
Read 7 tweets
May 4, 2022
COVID-19 vaccine elicited immune responses in Africa are understudied. We teamed up with The Nigerian Institute for Medical Research (NIMR) to examine AZ vaccine responses in the context of background prior infections and breakthrough infections.…
We first measured baseline SARS-CoV-2 seroprevalence prior to vaccination using flow cytometry methods for binding antibodies to nucleocapsid (N), coupled with virus neutralisation approaches for protective neutralizing antibody responses to VOC (January 2021)
In 140 participants, we found a high level - 62/140 (44%) of participants were previously infected with SARS-CoV-2 as evidenced by presence of Nucleocapsid (N) antibodies in early 2021 (N is absent from vaccines used in Nigeria, therefore presence indicates a past infection).
Read 14 tweets
Apr 29, 2022
Our paper on HIV-1 intrahost evolution under antiviral therapy out after >5 years in the making. @steveo_kemp R Goldstein, A Derache, @Tuliodna D Martin @CollinsIwuji ANRS TasP. Major implications for SARS-CoV-2 and resistance to therapeutics :…
Here we wanted to study HIV-1 evolution within individuals who were unable to suppress the virus with antiretroviral therapies. This was mainly due to sub optimal adherence to treatment, as drug levels in blood were measured and often low. Main findings:
1. Over periods of a year or more we observed significant changes in viral populations, with large fluctuations in synonymous and nonsynonymous variant frequencies despite stable viremia. Image
Read 7 tweets
Feb 2, 2022
Quick explainer on some of the key findings in our recent paper.…. We find Omicron spike binds ACE2 better than Delta. Both variants replicate similarly in nasal cell cultures, but in airway cells high in TMPRSS2 there was significant impairment for Omicron
Spike cleavage by furin proteases during virus production in cells allows spike to use TMPRSS2, a cell membrane protease. Omicron (grey) is impaired in cell entry relative to Delta (orange) and Wu-1 (black) when TMPRSS2 (T2) overexpressed; ACE2 (A2) levels impact effect size (R)
We found that consistent with impaired use of TMPRSS2, the Omicron spike was inefficiently cleaved (as shown by the ratio of S2:full length spike). This came as a surprise because Omicron has three mutations around the polybasic cleavage site.
Read 10 tweets

Did Thread Reader help you today?

Support us! We are indie developers!

This site is made by just two indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3/month or $30/year) and get exclusive features!

Become Premium

Don't want to be a Premium member but still want to support us?

Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal

Or Donate anonymously using crypto!


0xfe58350B80634f60Fa6Dc149a72b4DFbc17D341E copy


3ATGMxNzCUFzxpMCHL5sWSt4DVtS8UqXpi copy

Thank you for your support!

Follow Us on Twitter!